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Practical Ni-Catalyzed Aryl-Alkyl CrossCoupling of Secondary Redox-Active Esters Josep Cornella, Jacob T. Edwards, Tian Qin, Shuhei Kawamura, Jie Wang, ChungMao Pan, Ryan Gianatassio, Michael A. Schmidt, Martin D. Eastgate, and Phil S. Baran J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b00250 • Publication Date (Web): 02 Feb 2016 Downloaded from http://pubs.acs.org on February 2, 2016
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Journal of the American Chemical Society
Practical Ni-Catalyzed Aryl-Alkyl Cross-Coupling of Secondary Redox-Active Esters Josep Cornella,†§ Jacob T. Edwards,†§ Tian Qin,† Shuhei Kawamura,† Jie Wang,† Chung-Mao Pan,† Ryan Gianatassio,† Michael Schmidt,‡ Martin D. Eastgate,‡ Phil S. Baran†,* †
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037
‡
Chemical Development, Bristol-Myers Squibb, One Squibb Drive, New Brunswick, New Jersey 08903
Supporting Information Placeholder
ABSTRACT: A new transformation is presented that enables chemists to couple simple alkyl carboxylic acids with aryl zinc reagents under Ni-catalysis. The success of this reaction hinges on the unique use of redox-active esters that allow one to employ such derivatives as alkyl halides surrogates. The chemistry exhibits broad substrate scope and features a high degree of practicality. The simple procedure and extremely inexpensive nature of both the substrates and pre-catalyst (NiCl2·6H2O, ca. $9.5/mol) bode well for the immediate widespread adoption of this method.
complex acts as a single electron reductant to the pyridothione group. A. Context: Ni-catalyzed aryl-alkyl cross coupling reactions R1 [M] = B, Sn, Mg, Zn, Si Ar Ar [M] Ni cat.
X
R2 R1
Ar X
R2
X
Ar R1
Ni cat. [Weix, Gong Molander]
R1 R2
[Negishi, Kumada, Corriu, Kochi Knochel, Kambe, Fu, Biscoe, Hu]
[M]=BF 3K, Si(OR) 4Ar X or R1 CO2H Ni + Ir cat, hν [Doyle-MacMillan] Het [Molander]
Ni cat.
R2
[M] R1
H
Ni cat. [Chatani, Lei R 2 Ackermann, Hu]
[M]
R1
X
ZnCl Ni cat. [This work] Carboxylic acids as alkyl electrophiles
R2
X δ+
R1
R2
O
R1
synthon
RO R2 Practical and simple methods to forge linkages between sp2 and sp3 hybridized carbons are of extreme imB. Key Finding: Barton esters react with aryl-Ni complexes in the absence of light portance in every branch of chemical science.1 Thus far, DMF, 300W lamp Et O di-tBubipy 51% the majority of contributions in this arena have focused SPy Ph 3P Et N Bu Cl O on the use of alkyl halides or alkyl metal species for the Ni Bu Et Ph PPh 3 Bu S 54% sp3 component.2 Elegant demonstrations of the practical2 1a + 3 4 [LnNi] ity and feasibility of such a disconnection using nickel DMF, rt, no light hypothesis: catalysis (Figure 1A) can be found from the early examLn S O O Et [Ni] ples of Kumada,3 Corriu4, Kochi5 or Negishi,6 to the Et Et N + N O O most recent studies from the Kambe,7 Knochel,8 Fu,9 [– CO2] Bu Bu B Bu A S 10 11 C Biscoe and Hu labs (just to name a few). A recurring C. Invention: Ni-catalyzed cross-coupling of redox active esters with Ar-ZnCla Et O theme in the mechanistic picture in these reactions inO PhZnCl·LiCl (5, 3 equiv.) 20 mol% NiCl ·glyme volves a single-electron transfer (SET) based catalytic Et 2 Bu O N 40 mol% di-tBubipy cycle.12 Chatani13 and Weix14 have extended these radiBu THF:DMF (3:2), 25 ºC X 1g (1 equiv.) O 3 (92% isolated)e cal-based processes to the realms of directed C–H funcb [redox-active] entry yield (%) deviation from above N tionalization and cross-electrophile coupling. Recently, N X = 2-pyridothione, 1a 15 16 43 1 O the Molander, MacMillan, and Doyle groups reported N N 1a (150W Lamp) 43 2 Z X = Cl O < 1c 3 the coupling of alkyl boron or ammonium alkylsilicates S c 1b (Z = N, OAt) X = OMe
